Molecular genetic and structural studies of toxic shock syndrome toxin-1 (TSST-1) will be continued. Dr. Novick has shown that the determinant of TSST-1 (tstH) is carried by a site-specific transposon, Tn557, and analysis of the molecular genetics of Tn557 is proposed. He has found that the pathogenic activities of TSST-1 are localized to the N-terminal half of the molecule, the T cell mitogenicity to the C-terminal half. The precise nature of these determinants will be analyzed and contributory epitopes defined. TSST-1 is lethal for endothelial cells but stimulatory for T cells, suggesting that different types of receptors may be involved. TSST-1 receptors will be isolated from endothelial and T cells and compared. TSST-1 synthesis is growth phase-regulated and a mutational analysis of this regulation is proposed. Finally, the investigator has shown that the streptococcal toxic shock-like toxin, SpeA, is regulated similarly to TSST-1 and a mutational study of toxin regulation in Streptococcus pyogenes is planned.